DESCRIPTION Neurofibromatosis 2 (NF2) is a severe inherited disorder characterized by multiple nervous system tumors, particularly schwannomas and meningiomas. The cardinal feature of NF2 is the occurrence of bilateral schwannomas of the eighth cranial nerve and although benign, the manageability of these slow growing tumors often results in deafness, balance impairment and permanent nerve damage. The protein product of the NF2 gene, merlin, is a tumor suppressor named for its similarity to the moesin-, ezrin-, and radixin-like (ERM) family of proteins. The classification of merlin in the ERM family suggests a novel tumor suppressor role by acting as a signaling molecule in the pathway regulating actin cytoskeleton organization and determine if its dysfunction results in tumorigenicity. F-actin co-sedimentation assays will determine if merlin behaves as an ERM member by binding to actin, In actin-binding is indicated, merlin's effect on the kinetics of actin assembly will be assessed using pyrene-labeled actin; regulatory molecules effecting these events, such as phosphatidylinositol 4,5-biphosphate (PIP/2) and Ca/2+, will be defined; and merlin's actin binding site will be mapped. The identity and function of additional signaling factors, such as PDGF, Rho-GTPases, and PIP/2 will be established. Understanding the normal function of merlin the signal transduction pathway to actin filament assembly will be fundamental in determining NF2 neuropathology and ultimately, in devising therapeutic strategies for this devastating disease.